In vitro and in vivo activity of voriconazole and benznidazole combination on trypanosoma cruzi infection models

GULIN, JULIÁN ERNESTO NICOLÁS; EAGLESON, MACKENZIE ANNE; LÓPEZ-MUÑOZ, RODRIGO A.; SOLANA, MARÍA ELISA; ALTCHEH, JAIME; GARCÍA-BOURNISSEN, FACUNDO

ACTA TROPICA

ELSEVIER SCIENCE BV

Año: 2020 vol. 211

0001-706X

Combination therapy has been proposed as an ideal strategy to reduce drug toxicity and improve treatmentefficacy in Chagas disease. Previously, we demonstrated potent in vivo anti-Trypanosoma cruzi activity of voriconazole.In this work, we aimed to study the synergistic effect of voriconazole (VCZ) and benznidazole (BZ)both in vitro and in vivo models of T. cruzi infection using the Tulahuen strain. Combining VCZ and BZ at fixedconcentrations, the inhibitory concentration 50% (IC50) on amastigotes was lower than the obtained IC50 for BZalone and the Fractional Inhibitory Concentration Index (ΣFIC) suggested an in vitro additive effect on T. cruziamastigotes inhibition at concentrations devoid of cytotoxic effects. Treatment response in the in vivo model wasevaluated by comparing behavior and physical aspects, parasitemia and mortality of mice infected withTulahuen strain. VCZ and BZ treatments alone or in combination were well tolerated. All treated animals displayedsignificantly lower mean peak parasitemia and mortality compared to infected non-treated controls (p